Mesoporous silica nanoparticles boost aggressive cancer response to hydrophilic chlorin e6-mediated photodynamic therapy

Abstract

BackgroundChlorin e6 trisodium salt (Ce6) is a newly developed hydrophilic photosensitizer designed to mediate anticancer photodynamic therapy (PDT). The response of different cancer types and strategies to boost anticancer efficiency of Ce6-PDT are poorly studied.ObjectivesThis study aimed to investigate the response of different cancer types to Ce6-PDT, identify the unresponsive ones, and develop a nanosystem for response enhancement.MethodsSk-Br-3, MCF-7, U87, and HF-5 cells were tested in 2D cell cultures. Ce6 uptake, PDT-mediated phototoxicity, ROS production, caspase 3/7 levels, and cell death mode were examined. Furthermore, U87 spheroids were treated with Ce6-PDT. Mesoporous silica nanoparticles (MSN) were synthesized and loaded with Ce6. Cellular uptake and phototoxicity of MSN-Ce6 were compared to free Ce6 in vitro and in vivo.ResultsCe6 was detectable in the cell cytoplasm within 15 min. U87 cells showed the highest Ce6 cellular uptake. Upon Ce6-PDT, U87 cells were the most responsive ones with an 11-fold increase in ROS production. Here, 5 µM Ce6 and 4 J/cm2 were enough to reach IC50. Ce6-PDT induced both necrotic and caspase-dependent apoptotic cell death and 75% reduction of spheroids volume. Also, MCF-7 and HF-5 cells responded well to Ce6-PDT treatment. Sk-Br-3 breast cancer cells, on the other hand, were the least responsive ones with 80% viability after treatment (5 µM Ce6, 8 J/cm2). However, MSN-Ce6 conjugates increased Sk-Br-3 cellular uptake of Ce6 sevenfold decreasing the IC50 irradiation dose by an order of magnitude. In a very aggressive breast cancer rat model, MSN-Ce6-PDT treatment led to suppression of tumor volume by 50% and elevation of both Bax and caspase 3 by 90% compared to the control while the corresponding values for Ce6-PDT were 30% and 70%, respectively.ConclusionThe newly developed hydrophilic chlorin and even more its MSN conjugate show high activities in anticancer PDT.